Seminoma and a gonadoblastoma in an infant with mixed gonadal dysgenesis

Abstract

The genital examination of a newborn with ambiguous genitaliarevealedanenlargedphallicstructure,asingleanterior perineal opening, and fused labioscrotal folds with no palpable gonads (Fig 1). No Turner syndrome stigmata were present. The testosterone level was 29 ng/dL (normal range for female newborns, 20-64 ng/dL; males, 75-400 ng/dL), and a mullerian inhibitory substance was undetectable. Chromosome analysis revealed a 45,X/46,XY mosaic karyotype. A normal uterus and kidneys were identified by ultrasonogram, and a urogenital sinus was present on cystourethrogram. The family selected a female gender for the baby. At9monthsofage,theinfanthadbilateralgonadectomy and feminizing genital surgery. Intraoperative findings confirmed a low confluence urogenital sinus with a well-formed vagina. A streak gonad with a normal fallopian tube and hemiuterus were present on the right. The left gonad was torsed and free-floating in the abdomen without identifiable ductal structures. Pathologic examination of the right gonad showed a testis-streak with seminiferous tubules containing placental alkaline phosphatase-positive (PLAP) cells, consistent with intratubular germ cell neoplasia, and peripheral streak gonadal tissue with multifocal areas of gonadoblastoma (Fig 2, B). The left gonad consisted of an encapsulated 2.0 3 1.8 3 0.6 cm soft tissue mass with diffuse coagulative necrosis and dystrophic calcifications consistent with torsion. Sheets of monomorphic large round cells surrounded by fibrous septae (Fig 2, A) were identified, consistent with a seminoma. A computed tomography scan of the abdomen, pelvis, and chest showed no evidence of metastasis. Beta-human chorionic gonadatropin and a-fetoprotein levels were normal. We describe a unique case of bilateral gonadal tumors occurring in an infant with mixed gonadal dysgenesis (MGD). MGD is an intersex disorder characterized by asymmetric dysgenetic gonads, ambiguous genitalia, persistent mullerian structures, and a Y cell line. Patients with MGD are at high risk of developing gonadal tumors, the majority being identified in the second and third decade of life. The most common tumor is a gonadoblastoma, a benign lesion composed of dysplastic germ and sex cord cells. However, the germ cell element can give rise to malignant germinomas such as seminomas, as in our case. 1,2 Prophylactic gonadectomy is indicated, but there are no clear recommendations as to when this should occur. The young age of this child emphasizes the importance of very early gonadectomy in patients with MGD that are to be raised in the female gender, and careful monitoring of male infants after early orchiopexy.